We are interested in pursuing the biochemical identity and properties of non-specific humoral suppressor factor in the sera or body fluids of cancer patients. We have previously shown that the major immunosuppressive factor in malignancy may be antigenically related to the E-receptor of human peripheral blood T lymphocytes. During the past few years, we've been trying to delineate the biochemical relationship between the non-specific humoral suppressor factor and the cellular E-receptor derived from human peripheral blood T lymphocytes. Radioimmunoassay developed with monoclonal anti-E receptor antibody versus purified serum suppressor factor revealed that there is relatively large quantity of this factor (mg/ml range) in the sera of various patients as well as in normal human serum. Sandwich radioimmunoassay developed with detergent-solubilized, purified human T lymphocyte lysate indicated there is a relatively small quantity of the soluble form of cellular E-receptor in normal human serum (ng/nl range), although the levels of this soluble E-receptor are elevated in the sera of various autoimmune disease or cancer patients. Using 125I-labeled anti-E-receptor antibody, we also have studied the mechanism of induction of new E-receptor synthesis and its shedding into culture supernatants using various biological response modifiers. The T cell mitogen, phytohemagglutinin, and the tumor promoter, phorbol myristic acetate, both stimulate the synthesis and release new E-receptors whereas non-T cell mitogens, lipopolysaccharide or interleukins 1 and 2 failed to do so. IL 1, however, can augment lectin-induced E-receptor induction. We are in ther process of elucidating the amino acid sequence of the purified serum suppressor factor the amino sequence of E-receptor deduced from the cloned gene that codes for the E-receptor, for comparison of amino acid sequence homology.